According to the Cancer Atlas, lung cancer remains the major cancer among the 10.9 million new cases of cancer diagnosed annually worldwide. The mortality from lung cancer is greater than the combined mortality for breast, colon and prostate cancer combined. Most patients with metastatic non-small-cell lung cancer (NSCLC) are treated with platinum-based chemotherapy regimens. The drug combination of cisplatin and docetaxel is one of the commonly used regimens in metastatic NSCLC. Although both drugs are powerful disruptors of cell growth, positive therapeutic response rates to this therapy remain low for NSCLC patients, from 25% to 30%. While adding new biologics such as bevacizumab to the current treatment standard can improve treatment response, median survival for advanced NSCLC patients receiving this type of treatment remains low at under 12 months. Research studies have demonstrated that Vitamin D, and it's signaling pathways are important biological targets in cancer therapeutics. In vitro and in vivo calcitriol (1, 25 dihydroxycholcalciferol) is antiproliferative and potentiates the antitumor effects of cytotoxic agents (e.g. taxanes, platinum analogues). We have shown that administration of high doses of calcitriol and cisplatin is feasible and associated with complete tumor regressions in dogs with spontaneous cancers. Calcitriol has also shown to be synergistic with docetaxel both in preclinical as well as in a recent phase II clinical trial in prostate cancer. Based on these results and other supporting data from studies indicating that calcitriol functions as a potent and well tolerated anti-tumor agent when used in combination with drugs likes cisplatin and docetaxel, we hypothesize that introducing calcitriol into treatment regimes for NSCLC patients has the potential to demonstrably improve treatment response for these patients. The overall goals for conducting this phase I/II clinical study will be (1) to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of calcitriol in combination with cisplatin/docetaxel in patients with advanced NSCLC, (2) to assess the response rates of patients with advanced NSCLC to the combination of calcitriol with cisplatin/docetaxel, (3) to evaluate the pharmacokinetics (PK) of administering calcitriol intravenously at the MTD, and (4) to evaluate correlations between calcitriol PK and changes on specific coding regions of the gene associated with calcitriol breakdown.